This is a competitive renewal application from an inter-institutional group of investigators with long-standing interest in Angelman syndrome (AS), Rett syndrome (RTT), and Prader-Willi syndrome (PWS) to continue a Rare Diseases Clinical Research Center (RDCRC) within the Rare Diseases Clinical Research Network (RDCRN). The Center will focus on these three disorders based on the expectation that the near-term potential for meaningful therapy is strong. The specific aims for PWS are 1) to conduct longitudinal studies according to genotype, 2) to perform natural history studies on non-PWS individuals with early-onset morbid obesity (EMO) and compare them with PWS, and 3) to develop parameters and tool for clinical trials. A pilot project spanning the three disorders will examine the characteristics and patterns of sleep disorders, well-known accompaniments of each (funded by IRSF).The PWS sites will be at the University of Florida, University of Kansas, UC Irvine, and Vanderbilt University. The PWS RDCRC will utilize GCRCs in Gainesville, Irvine, Kansas City, and Nashville. The Center is expected to function synergistically with the Intellectual and Developmental Disability Centers-IDDRC (formerly the MRRC) at UAB, Kansas, and Vanderbilt. An extensive training program is proposed for stimulating the entry of new investigators into clinical research on rare diseases (funded by IRSF and PWSA). The Center will have active affiliation with and support from the Prader-Willi Syndrome Association (PWSA). A website for this RDCRC is available at www.circ.uab.edu. This site will be amplified to include a wide range of information for AS, RTT, and PWS.